Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study By UCSD Researchers Gives New Insight Into How Anthrax Bacteria Can Evade A Host’s Immune Response

07.01.2004


Biologists at the University of California, San Diego have determined how toxin produced by anthrax bacteria blocks a person’s normal immune response, a discovery that could lead to new treatments for anthrax infection.



In a paper to be published in the January 15th issue of The Journal of Immunology the UCSD scientists show why, in the presence of anthrax toxin, human immune cells fail to respond normally to lipopolysaccharide—a component of the cell walls of many bacteria including the bacteria that cause anthrax, Bacillus anthracis. Bacterial invasion, or the presence of lipopolysaccharide, usually causes immune cells known as macrophages to release cytokines—chemicals that signal other cells about the presence of an invader. Release of cytokines causes large numbers of immune cells to arrive at the site of infection and destroy the bacteria. By blocking this host immune response, anthrax bacteria are able to multiply unchecked. According to the Centers for Disease Control, approximately 75 percent of people infected with inhalation anthrax die, even with all possible supportive care including appropriate antibiotics.

“Although it was known for quite some time that anthrax toxins can suppress cytokine production, the mechanism by which Bacillus anthracis escapes the immune response isn’t really understood,” says Michael David, a biology professor at UCSD who headed the research team. “We have identified a protein molecule targeted by the anthrax toxin and determined where it acts in the sequence of steps involved in immune response.”


Macrophages have special receptors on their surfaces that bind to lipopolysaccharide. The binding of lipopolysaccharide to this receptor sets off a sequence of events inside the macrophage, in which a series of proteins activate one another in turn. This cascade of proteins activating one another ultimately turns on cytokine genes, causing the macrophage to churn out large quantities of cytokines.

It turns out that there are two separate, sometimes cooperating, routes in the cell by which series of proteins activate one another to switch on production of cytokines. One of the routes has been recognized for a long time, but researchers were sometimes puzzled when cytokine production was turned on or off without the proteins along this route being activated or deactivated. This puzzle was resolved when the David group and other groups simultaneously identified the second route, the IRF3 pathway. The anthrax toxin targets the IRF3 pathway by cleaving MKK6—one of the proteins in the series along the route. The cleavage of MKK6 prevents the cytokine genes from being switched on.

When the researchers made mutant macrophages with a variant of MKK6 that could not be cleaved by the anthrax toxin, these macrophages responded to lipopolysaccharide by producing cytokines even in the presence of the anthrax toxin. This suggests that developing a drug that could protect MKK6 and prevent anthrax toxin from cleaving it could help to prevent an anthrax infection from getting out of control. The anthrax bacteria would be unable to evade the normal immune response.

“While these results may not lead to a drug to cure anthrax in the next six months, the more you understand about bacteria and how they target the immune response the more options you have for developing drugs to treat the infections,” says David.

Previous work by other researchers has suggested that anthrax toxin evades the immune system by killing macrophages; however, according to David, cell death does not fully explain how anthrax bacteria evade the immune system.

“Only some types of macrophages are killed by anthrax toxins, but anthrax toxins diminish the production of cytokines in all of the macrophages we have tested,” David explains. “Also, less toxin is needed to shut off the immune response than to kill the macrophages.”

The other UCSD researchers involved with this project were Oanh Dang, a former graduate student in the David laboratory and the first author of the paper; Lorena Navarro, a former graduate student in the David laboratory and first author on two other papers that initially identified the IRF3 immune response pathway; and Keith Anderson, a technician in the David laboratory. This work was supported by a grant from the National Institutes of Health.


Media Contacts: Sherry Seethaler (858) 534-4656
Comment: Michael David (858) 822-1108

Sherry Seethaler | UC - San Diego
Further information:
http://ucsdnews.ucsd.edu/newsrel/science/santhrax.asp

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>